187 research outputs found
Mediating Roles of Emotion Regulation Difficulties and Rejection Sensitivity in the Relation Between Romantic Attachment and Couple Adjustment
Bağlanma kuramına göre gelişimin erken dönemindeki ilişkiler çerçevesinde hem duygu düzenlemeye ilişkin beceriler kazanılmakta hem de reddedilmeye karşı duyarlı bir örüntü gelişebilmektedir. Erken dönemdeki bu deneyimler aynı zamanda yetişkinlik dönemindeki bağlanma stilleri için
de belirleyici bir etkiye sahiptir. Çiftler arasındaki uyumun şekillenmesinde ve sürdürülmesinde
bağlanmanın önemli etkileri bulunmaktadır. Bu çalışma çift uyumunu belirleyebileceği düşünülen
bu değişkenlerin etkisini incelemeyi amaçlamıştır. Çalışmanın bir diğer hedefi reddedilme hassasiyetinin ve duygu düzenlemenin aracılık etkilerinin incelenmesidir. Örneklem, İstanbul ilinde yaşayan 346 evli bireyden oluşmaktadır (Nkadın = 173, Nerkek = 173). Yol analizine ilişkin bulgular, romantik bağlanmanın kaçınma boyutunun ve duygu düzenleme güçlüğünün çift uyumunu negatif
yönde yordadığını göstermektedir. Aracılık analizinin bulguları bağlanma kaygısındaki artışın
duygu düzenleme güçlüğünü artırdığını ve bunun da çiftlerin arasındaki uyumu azalttığını göstermektedir. Duygu düzenleme güçlüğü, kaygılı bağlanma örüntüsü ile çift uyumu arasındaki ilişkide
tam aracı etki göstermektedir. Bağlanmanın kaygı ve kaçınma boyutlarının reddedilme hassasiyetini artırdığı fakat reddedilme hassasiyetinin çift uyumu üzerinde doğrudan veya dolaylı bir etkisinin olmadığı görülmektedir. Sonuç olarak, çalışmanın bulguları bağlanma kuramını desteklemekte
ve erken dönem oluşan yapıların yetişkinlikte romantik ilişkileri etkilemeye devam ettiğini göstermektedir. Bulgulardan hareketle, duyguları düzenlemeye yönelik terapötik müdahalelerin evli bireylerin ilişki kalitesine olumlu katkı sağlaması beklenmektedir.According to the attachment theory, relationships in early developmental stages provide a basis for
emotion regulation skills and a pattern for rejection sensitivity. These early experiences also create
a tendency for specific attachment styles in adulthood. Attachment shapes and maintains adjustment between couples. The current study aimed to examine the relationship between attachment,
emotion regulation, and rejection sensitivity, which are thought to determine couple adjustment.
Another aim was to investigate the mediating effects of rejection sensitivity and emotion dysregulation. The participants consist of 346 married individuals living in the city of Istanbul (Nfemale =
173, Nmale = 173). Findings regarding the path analysis show that the avoidance dimension of romantic attachment and the difficulty in emotion regulation negatively predicted the dyadic adjustment. The findings of the mediation analysis revealed an increase in attachment anxiety amplified
the difficulty in emotion regulation and that decreased adjustment between the couples. Emotion
regulation difficulty fully mediated the relationship between anxious attachment pattern and couple
adjustment. Anxiety and avoidance dimensions of attachment were associated with increases in
rejection sensitivity. However, rejection sensitivity did not have a direct or indirect effect on couple
adjustment. In conclusion, the findings showed early structures continued to influence romantic
relationships in adulthood. Based on the findings, therapeutic interventions to regulate emotions
were expected to contribute positively relationship quality of couples
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Human Papillomavirus E6 Triggers Upregulation of the Antiviral and Cancer Genomic DNA Deaminase APOBEC3B
ABSTRACT Several recent studies have converged upon the innate immune DNA cytosine deaminase APOBEC3B (A3B) as a significant source of genomic uracil lesions and mutagenesis in multiple human cancers, including those of the breast, head/neck, cervix, bladder, lung, ovary, and other tissues. A3B is upregulated in these tumor types relative to normal tissues, but the mechanism is unclear. Because A3B also has antiviral activity in multiple systems and is a member of the broader innate immune response, we tested the hypothesis that human papillomavirus (HPV) infection causes A3B upregulation. We found that A3B mRNA expression and enzymatic activity were upregulated following transfection of a high-risk HPV genome and that this effect was abrogated by inactivation of E6. Transduction experiments showed that the E6 oncoprotein alone was sufficient to cause A3B upregulation, and a panel of high-risk E6 proteins triggered higher A3B levels than did a panel of low-risk or noncancer E6 proteins. Knockdown experiments in HPV-positive cell lines showed that endogenous E6 is required for A3B upregulation. Analyses of publicly available head/neck cancer data further support this relationship, as A3B levels are higher in HPV-positive cancers than in HPV-negative cancers. Taken together with the established role for high-risk E6 in functional inactivation of TP53 and published positive correlations in breast cancer between A3B upregulation and genetic inactivation of TP53, our studies suggest a model in which high-risk HPV E6, possibly through functional inactivation of TP53, causes derepression of A3B gene transcription. This would lead to a mutator phenotype that explains the observed cytosine mutation biases in HPV-positive head/neck and cervical cancers
Tannin- caprolactam and Tannin- PEG formulations as outdoor wood preservatives: Weathering properties
International audienceAbstractKey messageThis article presents the leaching, fire and weathering resistance improvements of samples treated with tannin-based wood preservatives added of caprolactam. PEG-added formulations show limited applicability. The FT-IR and13C-NMR analyses of the caprolactam-added formulations show some evidences of copolymerization.ContextTannin-boron wood preservatives are known for their high resistance against leaching, biological attacks, fire as well as for the good mechanical properties that they impart to wood. These properties promoted these formulations for being a candidate for the protection of green buildings. However, the low elasticity of these polymers and their dark colour implied limited weathering resistances.AimsThe aim of the study is to find suitable additives for tannin-based formulations to overcome their limited weathering resistances, without compromising the other properties.MethodsTreatment, leaching and fire tests, dimensional stability as well as artificial and natural weathering of the timber treated with caprolactam-added and PEG-added formulations were performed. FT-IR and 13C-NMR of the formulations were presented.ResultsThe presence of caprolactam improved the properties of the formulation with particularly significant results in terms of resistance against leaching and dimensional stability. These enhancements were imparted also to the weathering resistance of the tannin-caprolactam formulations. Indeed, the colour changes during the artificial and natural exposures were stable for longer periods. FT-IR and 13C-NMR investigations of the advanced formulations were led, and covalent copolymerization of the caprolactam with the tannin-hexamine polymer was observed.ConclusionThe tannin formulations with caprolactam improved the durability of the wood specimens, while the PEG-tannin presented strong application drawbacks
Novel and Recurrent Mutations of WISP3 in Two Chinese Families with Progressive Pseudorheumatoid Dysplasia
BACKGROUND: The WNT1-inducible signaling pathway protein 3 (WISP3), which belongs to the CCN (cysteine-rich protein 61, connective tissue growth factor, nephroblastoma overexpressed) family, is a secreted cysteine-rich matricellular protein that is involved in chondrogenesis, osteogenesis and tumorigenesis. WISP3 gene mutations are associated with progressive pseudorheumatoid dysplasia (PPD, OMIM208230), an autosomal recessive genetic disease that is characterized by the swelling of multiple joints and disproportionate dwarfism. METHODOLOGY/PRINCIPAL FINDINGS: Four PPD patients from two unrelated Chinese families were recruited for this study. The clinical diagnosis was confirmed by medical history, physical examinations, laboratory results and radiological abnormalities. WISP3 mutations were detected by direct DNA sequence analysis. In total, four different mutations were identified, which consisted of two missense mutations, one deletion and one insertion that spanned exons 3, 5 and 6 of the WISP3 gene. One of the missense mutations (c.342T>G/p.C114W) and a seven-base pair frameshift deletion (c.716_722del/p.E239fs*16) were novel. The other missense mutation (c.1000T>C/p. S334P) and the insertion mutation (c.866_867insA/p.Q289fs*31) had previously been identified in Chinese patients. All four cases had a compound heterozygous status, and their parents were heterozygous carriers of these mutations. CONCLUSIONS/SIGNIFICANCE: The results of our study expand the spectrum of WISP3 mutations that are associated with PPD and further elucidate the function of WISP3
Identifying allosteric fluctuation transitions between different protein conformational states as applied to Cyclin Dependent Kinase 2
BACKGROUND: The mechanisms underlying protein function and associated conformational change are dominated by a series of local entropy fluctuations affecting the global structure yet are mediated by only a few key residues. Transitional Dynamic Analysis (TDA) is a new method to detect these changes in local protein flexibility between different conformations arising from, for example, ligand binding. Additionally, Positional Impact Vertex for Entropy Transfer (PIVET) uses TDA to identify important residue contact changes that have a large impact on global fluctuation. We demonstrate the utility of these methods for Cyclin-dependent kinase 2 (CDK2), a system with crystal structures of this protein in multiple functionally relevant conformations and experimental data revealing the importance of local fluctuation changes for protein function. RESULTS: TDA and PIVET successfully identified select residues that are responsible for conformation specific regional fluctuation in the activation cycle of Cyclin Dependent Kinase 2 (CDK2). The detected local changes in protein flexibility have been experimentally confirmed to be essential for the regulation and function of the kinase. The methodologies also highlighted possible errors in previous molecular dynamic simulations that need to be resolved in order to understand this key player in cell cycle regulation. Finally, the use of entropy compensation as a possible allosteric mechanism for protein function is reported for CDK2. CONCLUSION: The methodologies embodied in TDA and PIVET provide a quick approach to identify local fluctuation change important for protein function and residue contacts that contributes to these changes. Further, these approaches can be used to check for possible errors in protein dynamic simulations and have the potential to facilitate a better understanding of the contribution of entropy to protein allostery and function
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The role of APOBEC3B in lung tumor evolution and targeted cancer therapy resistance
In this study, the impact of the apolipoprotein B mRNA-editing catalytic subunit-like (APOBEC) enzyme APOBEC3B (A3B) on epidermal growth factor receptor (EGFR)-driven lung cancer was assessed. A3B expression in EGFR mutant (EGFRmut) non-small-cell lung cancer (NSCLC) mouse models constrained tumorigenesis, while A3B expression in tumors treated with EGFR-targeted cancer therapy was associated with treatment resistance. Analyses of human NSCLC models treated with EGFR-targeted therapy showed upregulation of A3B and revealed therapy-induced activation of nuclear factor kappa B (NF-κB) as an inducer of A3B expression. Significantly reduced viability was observed with A3B deficiency, and A3B was required for the enrichment of APOBEC mutation signatures, in targeted therapy-treated human NSCLC preclinical models. Upregulation of A3B was confirmed in patients with NSCLC treated with EGFR-targeted therapy. This study uncovers the multifaceted roles of A3B in NSCLC and identifies A3B as a potential target for more durable responses to targeted cancer therapy.</p
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